Pulmonary hypertension: a paradigm for rare pulmonary diseases

Abstract

@ERSpublicationsPulmonary hypertension has become a paradigm for a successful approach to rare diseases in the respiratory field http://ow.ly/7y3l30gN0hqCite this article as: Harari S. Pulmonary hypertension: a paradigm for rare pulmonary diseases. Eur Respir Rev 2017; 26: 170120 [https://doi.org/10.1183/16000617.0120-2017. This year's final issue of the European Respiratory Review (ERR) features a series of articles on pulmonary hypertension, selected from some of the contributions presented in March 2017 in Vienna (Austria) at the Pulmonary Hypertension Forum organised yearly by Actelion Pharmaceuticals Ltd (Allschwil, Switzerland). A reader might wonder why our journal, like many others in the respiratory and cardiological fields, dedicates so much attention to pulmonary hypertension (an important but rare condition) compared to more common diseases. The answer lies in the great advances that research has made in this field over the last two decades. These advances have been translated into a real revolution in the approach to the disease and the patients, with important improvements in prognosis and quality of life, as already highlighted in a recent editorial [1]. Thanks to the joint efforts of the medical community and of the industry, in a healthy and transparent collaboration, pulmonary hypertension has become both an example and a paradigm of a successful approach to rare diseases, with the development of new effective drugs, the involvement of patient associations, and attention raised among the scientific community, which is often focused on less complex and more widespread diseases.In the respiratory field, another disease seems to be closely following the steps of pulmonary hypertension, namely idiopathic pulmonary fibrosis (IPF), which, together with other fibrosing lung diseases, represents a group of conditions that regularly attracts the interest of researchers and specialists, as well as of an increasingly strong and cohesive international scientific community. However, it is still too early to predict whether the results in IPF will be as successful as they have been in pulmonary hypertension.In this issue of the ERR, outstanding experts from around the world discuss pulmonary hypertensive conditions. In their review, HEMNES and HUMBERT [2] investigate some lesser-known pathobiological pathways responsible for the development of pulmonary arterial hypertension (PAH), outside the three better-known systems of nitric oxide, endothelin and prostacyclin. Indeed, these newly recognised pathways could become targets for the development of new drugs in the near future. CHAN and RUBIN [3] describe the metabolic mechanisms that are known to be dysregulated in pulmonary hypertension, by exploring advances in diagnostic testing and imaging modalities currently under development to improve the capability to efficiently diagnose this disease. They also discuss emerging drugs targeting these

Sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A Phase IIb, randomised, double-blind, placebo-controlled study – Rationale and study design

“…Results of previous clinical trials of sildenafil in PH in the context of IPF have generally been inconclusive, possibly owing to their small sample sizes, short observation periods, imprecise definitions of study populations or primary endpoint selection [29][30][31][32][33][34]. In the STEP-IPF trial, sildenafil was studied in a cohort of 180 patients with advanced IPF (defined as diffusing capacity for carbon monoxide [DLCO] < 35% predicted) who were expected to have a high prevalence of PH.…”

Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra

“…Sildenafil is a PDE 5A (PDE‐5) inhibitor that stabilizes cGMP, the secondary messenger for the pulmonary vasodilator NO, and is approved for the treatment of PAH (Hoeper & Welte, 2006) but not PH in the context of significant pulmonary parenchymal disease. Previous clinical trials of sildenafil use in IPF failed to meet the endpoints, largely due to small sample size, short observation period, poorly defined study population, or poor primary endpoint selection (Collard, Anstrom, Schwarz, & Zisman, 2007; Ghofrani et al, 2002; Han et al, 2013; Harari, 2012; Jackson et al, 2010; Zisman et al, 2010).…”

Incidence and outcomes of pulmonary hypertension in the Ireland

“…Our understanding of the pathobiology, pathophysiology and epidemiology of PAH has evolved in recent years 5. Similarly, treatment options have expanded and PH has become a paradigm for a successful approach to rare respiratory diseases 6. The transforming landscape of PH will have implications for disease incidence and patient outcomes.…”